Pharmacology
NSAIDs, acetaminophen & non-opioid analgesics
Pharmacology

NSAIDs, acetaminophen & non-opioid analgesics

Mechanism (COX-1 vs COX-2), GI/renal/cardiac risks, aspirin dosing tiers, APAP toxicity, adjuvant analgesics.

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◆NSAID classes

  • •Non-selective (ibuprofen, naproxen, indomethacin, diclofenac, ketorolac) — block COX-1 + COX-2
  • •COX-2 selective (celecoxib) — less GI but ↑ cardiovascular risk (rofecoxib pulled from market)
  • •Aspirin: irreversible COX inhibitor (rest of NSAIDs reversible)

◆Aspirin tiers by dose

  • •81 mg/day — antiplatelet (cardio-protective in secondary prevention; primary controversial)
  • •325–650 mg PRN — analgesic / antipyretic
  • •650 mg q4h or higher — anti-inflammatory (rheum diseases historically)
  • •Acute MI: 325 mg CHEWED at presentation
  • •TIA / stroke: 81–325 mg/day (after exclude hemorrhage)

◆Side effects of NSAIDs

  • •GI: ulcer, bleeding, perforation — ↑↑ with steroid co-use, anticoagulation, age >60, prior PUD
  • •PPI prophylaxis if ≥2 GI risk factors
  • •Renal: AKI (vasoconstriction of afferent arteriole), interstitial nephritis, papillary necrosis
  • •↓ ACE-I/ARB/diuretic efficacy + ↑ BP
  • •Cardiovascular: ↑ MI/stroke risk (except aspirin) — esp diclofenac, COX-2 selective
  • •Bronchospasm in aspirin-sensitive asthma (Samter triad: asthma + nasal polyps + ASA sensitivity)
  • •Reye syndrome — AVOID aspirin in viral illness in children
  • •Bleeding (irreversible with aspirin × 7–10 days; reversible with others)
  • •Premature closure of ductus arteriosus in pregnancy after 30 wks (avoid in 3rd trimester)

◆Acetaminophen (APAP)

  • •Mechanism: weak central COX inhibitor + other actions
  • •GOOD: no GI/renal toxicity, no antiplatelet effect, safe in pregnancy
  • •BAD: hepatotoxic in overdose (>4 g/day in healthy adults; less in alcoholic/malnourished)
  • •Antidote: N-acetylcysteine (NAC); follow Rumack-Matthew nomogram
  • •Phases: 1 (0–24 hr) asymptomatic, 2 (24–72) RUQ pain + ↑ AST/ALT, 3 (72–96) fulminant hepatic failure
  • •Combined products (Percocet, Vicodin) — watch APAP totals to avoid hepatotoxicity

◆Adjuvant analgesics (neuropathic pain, chronic pain)

  • •Gabapentin, pregabalin — diabetic neuropathy, postherpetic neuralgia; weight gain, sedation
  • •TCAs (amitriptyline, nortriptyline) — neuropathic pain, migraine prophylaxis; anticholinergic
  • •SNRIs (duloxetine, venlafaxine) — fibromyalgia, diabetic neuropathy, depression with pain
  • •Topical lidocaine — postherpetic neuralgia, focal neuropathy
  • •Topical capsaicin — burning sensation initially, then desensitization
  • •Carbamazepine — trigeminal neuralgia (first-line)

High-yield pearls

  • ◆Aspirin + viral illness in kids = Reye syndrome → use ibuprofen or APAP instead
  • ◆NSAID + ACE-I + diuretic = 'triple whammy' AKI risk
  • ◆Ketorolac max 5 days (renal + GI risk with longer use)
  • ◆Aspirin-exacerbated respiratory disease (Samter triad): aspirin + asthma + nasal polyps → use leukotriene modifiers or biologics
  • ◆APAP overdose: NAC before phase 3 (72 hr) prevents most hepatotoxicity
  • ◆Carbamazepine for trigeminal neuralgia (NOT NSAIDs)
  • ◆Pregnancy + NSAIDs after 30 weeks = premature PDA closure + oligohydramnios — use APAP
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